1. Field of the Invention
The present invention generally relates to implantable cardiac devices, including pacemakers, defibrillators and cardioverters, which stimulate cardiac tissue electrically to control the patient's heart rhythm. More particularly, the present invention relates to a method and apparatus for a three-chamber implantable pacemaker or defibrillator to treat heart failure with cardiac dysynchrony.
2. Description of the Related Art
Cardiac resynchronization therapy (CRT) is a proven technique for treating drug refractory heart failure (HF) with cardiac dyssynchrony. By delivering properly timed left ventricular (LV) pacing, CRT can pre-excite the LV region that otherwise would show delayed activation, thus correcting the intra-ventricular dysynchrony. In addition, by delivering properly timed right ventricular (RV) pacing with respect to the LV pacing, the inter-ventricular dyssynchrony can also be corrected. Improving the intra-ventricular and inter-ventricular synchrony, CRT can effectively improve the hemodynamic performance of the heart, leading to improvement in cardiac contractility and cardiac output. Growing evidence suggests that CRT can result in reverse remodelling of the heart, manifested by reduced mitral regurgitation, reduced end-systolic and end-diastolic volume of the LV, and improved ejection fraction (EF). Consequently, CRT has been shown to improve the longevity and quality of life of the HF patients.
However, despite its great success, clinical experience has shown that about one third of the CRT candidates are non-respondents. There are many possible explanations for the non-responsiveness, including inappropriate LV lead location, non-optimal A-V delay and V-V delay settings, etc. Particularly, the inappropriate LV lead location is considered one of the most important factors that contribute to reduced CRT efficacy. Preferably, the LV pacing should pre-excite the LV myocardium with the most delayed intrinsic activation. However, in many cases, due to the difficulty to implant the LV lead through the coronary sinus, the LV lead could not be placed in such target location. As a result, the LV pacing could not correct the delayed LV activation of that region, thus the intra-ventricular dysynchrony remains. In other circumstances where patient has ischemic heart disease, the LV pacing electrode may overlay or near the myocardial infarct region which either does not respond to LV pacing or could not conduct properly the electrical activation.
To solve this problem, several approaches have been attempted on multi-site LV pacing, based on the concept that simultaneous activation of larger myocardial volume could improve the intra-ventricular synchrony. For example, Lenarczyk et al. investigated the feasibility of triple-site (double LV and single RV) pacing for treating HF patients. The response rate after 3 months triple-site CRT was higher than 95%. Recently, Yoshida et al. examined the effect of CRT by triangle ventricular (Tri-V) pacing at RV apex, RV outflow tract, and the LV. In acute settings, they showed that Tri-V significantly improved HF patients' LV function with better resynchronization effects compared with conventional biventricular pacing. Multi-site LV pacing system was also disclosed in U.S. Pat. Appl. No. 2005/0055058 by Mower. In addition, a method and apparatus for linear stimulation of the heart using an elongated electrode or plurality of electrodes were also disclosed in U.S. Pat. No. 6,829,506 issued to Pastore et al. However, implantation of multiple leads is technically challenging, requires longer procedure duration and fluoroscopy time, and may lead to higher complication rate. Design of CRT system with multiple electrodes for LV pacing not only requires special lead design, but also requires fundamental change of the hardware and firmware of the implant device.
Although conventional cardiac pacing uses cathodal stimulation, it has been shown that anodal stimulation can also reliably depolarize the cardiac tissue. The underlying mechanism has been explained by the virtual electrode theory. On one hand, a strong, short anodal pacing pulse can hyperpolarize a “dog bone” shaped region of the myocardial tissue underlying the stimulation electrode (virtual anode). On the other hand, depolarization can occur at virtual cathodes adjacent to the virtual anode (a,k.a., anodal make stimulation).
Virtual electrode theory has been used to examine the basic mechanisms of cardiac pacing such as the factors affecting the stimulation threshold and pace/shock termination of ventricular tachyarrhythmia. Recently, several clinical observations on cardiac pacing have also been explained by the virtual electrode theory. Tedrow et al. and Sauer et al. independently showed that increasing LV pacing amplitude can produce a larger virtual electrode, which can result in capture of a larger myocardial area, and reduce the conduction time from LV to RV. Lloyd et al. demonstrated that CRT with anodal LV pacing can significantly improve the LV function compared to conventional CRT with cathodal LV pacing. The underlying mechanism was thought to be larger area of direct activation by the virtual cathode than the cathodal pacing.
Anodal stimulation has also been suggested for implantable pacing systems. For example, in U.S. Pat. No. 5,800,464 issued to Kieval, it was disclosed that properly timed sub-threshold anodal stimulation might hyperpolarize the myocardial cells of a heart chamber to enhance the relaxation thereof in the diastolic phase and to thereby enhance cardiac function. In U.S. Pat. No. 5,814,079 also issued to Kieval, it was further disclosed that the properly timed anodal stimulation might prevent cardiac arrhythmia by suppressing aberrant electrical activity, and might also convert the detected tachyarrhythmia. However, these hypotheses have never been supported by clinical evidence. In addition, the so-called proper timing and proper strength of the anodal stimulation as required in above patents are not easy to maintain in the implantable pacing device. In U.S. Pat. No. 6,342,232 and U.S. Pat. App. No. 2005/0055058 both issued to Mower, a biphasic stimulation method was disclosed, whereby a sub-threshold anodal stimulation is applied followed by a cathodal stimulation. The subthreshold anodal stimulation, by hyperpolarizing the cardiac cells, acts as a conditioning mechanism to improve conduction through the heart muscle. Evidently, the sub-threshold anodal stimulation was never intended for myocardial capture. The increase of conduction speed in the local myocardial sites by anodal pacing does not necessarily translate to improvement in cardiac mechanical synchrony or cardiac function.
In view of above, there is a need for an implantable cardiac pacing system that can depolarize multiple regions of the heart nearly simultaneously to improve the effectiveness of the CRT.